Several lines of evidence implicate fetal exposure to prenatal hazards, including maternal stress, in the etiology of schizophrenia. Complementary research suggests schizophrenia may involve neuropsychological deficits due to disturbances in early brain development. The long-term goal of this project is to pioneer a new research strategy for investigating associations between prenatal stress and risk of developing neuropsychiatric problems, particularly schizophrenia. This strategy makes use of "natural experiments" (severe natural disasters striking heavily populated areas) that provide a source of maternal stress that is time-limited and occurs with little warning, is externally imposed (difficult to dismiss as an epiphenomenon of parental characteristics, and is severe (natural disasters are one of the few events rated on DSM-III-R Axis IV as a more severe psychological stressor than loss of one's spouse). The natural disaster for the proposed pilot study will be the 1953 Worcester, MA, tornado -- one of the deadliest in American history -- that has several characteristics of natural disasters that research indicates tend to produce particularly stressful experiences. The tornado struck heavily populated neighborhoods which (a) had a high percentage of young couples, and (b) are located an hour's drive from our laboratory. The specific aim is to conduct a pilot study whose research design has two complementary aspects. The first aspect is to determine the feasibility of this new research strategy. The second aspect is to test the hypotheses that both (a) interview-based DSM-III-R diagnoses of schizophrenia and (b) neuropsychological deficits consistent with higher- order cortical dysfunction are significantly increased in subjects exposed to stress prenatally. Birth records will be checked to identify approximately 120 "index" subjects exposed in utero, to maternal stress caused by the tornado, and 120 "control" subjects exposed to the same disaster during infancy. Subjects will be followed up and given a research diagnostic interview (SCID) and neuropsychological tests sensitive to cognitive deficits that are especially prominent in schizophrenia (Wisconsin Card Sort and Trail Making tests). Mothers will also be interviewed to help assess the stressfulness of their experience with the tornado. Statistical power tests indicate high likelihood of detecting effects similar in size to those in previous studies finding more schizophrenia in offspring of mothers stressed while pregnant.